Efficacy & Safety of Fluoroquinolone-Based Brucellosis Regimens (BRUCE)
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age16-75
SponsorThe First Affiliated Hospital of Shihezi University
About this trial
Brucellosis is a globally distributed zoonosis with persistent clinical management challenges. The World Health Organization(WHO)-recommended doxycycline-rifampin (DOX-RIF) dual regimen may drive rifampin-associated antimicrobial resistance across all brucellosis-endemic regions. Patients with osteoarticular brucellosis require long-term intravenous ceftriaxone triple therapy, which is linked to poor treatment adherence due to repeated hospital visits and outpatient care demands. Fluoroquinolones (levofloxacin \[LVX\], moxifloxacin \[MXF\]) exert excellent anti-Brucella activity and superior bone-joint penetration, yet high-quality multicenter prospective data comparing rifampin-sparing LVX-DOX/MXF-DOX dual regimens against standard RIF-DOX remain rarely reported. Existing comparative studies are limited to small single-center retrospective cohorts or trials pairing rifampin with fluoroquinolones rather than rifampin-free dual oral therapy. This multicenter prospective parallel-cohort protocol includes Module I (non-inferiority design) : 200 patients with uncomplicated acute brucellosis receiving 6-week dual oral therapy; and Module II (non-inferiority design) : 150 patients with imaging-confirmed osteoarticular brucellosis receiving 12-week triple therapy. Clinical data of standardized clinical, laboratory, radiologic, and subsequent longitudinal follow-up data will be collected via centralized electronic data capture. Primary endpoints include clinical and microbiological cure rates at 6 weeks (Module I) and 12 weeks (Module II). Secondary endpoints measure 24-week post treatment recurrence, 24- and 48-week radiologic improvement for osteoarticular disease, and adverse events during treatment. Multivariate regression and Cox models will identify independent prognostic factors and construct a generalizable recurrence risk prediction model. This clinical trial fills a critical evidence gap for oral fluoroquinolone-based regimens, with findings intended to supply supplementary brucellosis treatment approach, reduce rifampin resistance pressure, and eliminate reliance on prolonged parenteral therapy for complicated brucellosis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
The diagnostic basis for confirmed cases of brucellosis is the "Expert Consensus on the Diagnosis and Treatment of Brucellosis" published by the Editorial Board of the Chinese Journal of Infectious Diseases in 2017 and the "Diagnosis and Treatment Protocol for Brucellosis (2023 Edition)".
There is an epidemiological history, such as a history of contact with suspected or confirmed animals, patients, contaminated animal products, or cultures; living in an endemic area of brucellosis; or having a close relationship with the production, use, and research of vaccines.
At the same time, there are the following relevant clinical manifestations: fever, hyperhidrosis, joint pain, headache, fatigue, anorexia, myalgia, weight loss, arthritis, spondylitis, meningitis, or focal organ involvement such as endocarditis, hepatosplenomegaly, orchitis, or epididymitis.
In the serological screening, the Rose Bengal plate agglutination test is positive. For the tube agglutination test (SAT), the titer is 1:100 or higher with significant agglutination, or if the course of the disease is more than one year, the titer is 1:50 with significant agglutination or higher; or if there is a history of brucellosis vaccination within half a year, the titer reaches 1:100 with significant agglutination or higher. Accompanied by (or) positive culture of Brucella in the patient's blood, body fluids, or tissues. Or positive NGS detection of Brucella.
Disqualifiers
Those with comorbid tuberculosis, severe cardiopulmonary dysfunction, advanced tumors, central nervous system diseases (such as a history of epilepsy), or other systemic diseases; 2. Those with comorbid neurological or mental disorders who are unable or unwilling to cooperate; 3. Pregnant or lactating women, or those with a recent plan to have children; 4. Patients with a history of using glucocorticoids, immunomodulators, anti - tuberculosis drugs, etc. within the past 3 months; 5. Patients with missing important information or abnormal mental states.
Trial design
Design model
Parallel
Treatments tested in this trial
Doxycycline + Rifampicin
DrugStandard first-line dual oral regimen recommended by WHO for brucellosis. Eligible patients with uncomplicated brucellosis take oral doxycycline combined with rifampicin continuously for an 8-week course.
Doxycycline + Levofloxacin
DrugExperimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with levofloxacin for a total of 8 weeks.
Doxycycline + Moxifloxacin
DrugExperimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with moxifloxacin for a total of 8 weeks.
Doxycycline + Rifampicin + Ceftriaxone (intravenous therapy for 4 weeks)
DrugTriple combined regimen for moderate-severe osteoarticular brucellosis. Patients take oral doxycycline and rifampicin continuously, plus 4 weeks of intravenous ceftriaxone infusion. The scheme targets complicated joint and bone lesions to strengthen antibacterial efficacy for severe cases.
Triple oral regimen (Doxycycline + Rifampicin + Levofloxacin)
DrugFull-course oral triple regimen for brucellosis treatment. Patients continuously take oral doxycycline, rifampicin and levofloxacin for 8 weeks. This regimen boosts antibacterial potency against bone-joint brucellosis lesions and lowers rifampicin resistance risks compared with dual-drug schemes.
Triple oral regimen (Doxycycline + Rifampicin + Moxifloxacin)
DrugFull-course oral triple regimen for brucellosis therapy. Patients take oral doxycycline, rifampicin and moxifloxacin daily for an 8-week treatment cycle. Moxifloxacin delivers outstanding bone-joint tissue penetration, enhancing curative effects for osteoarticular brucellosis and reducing rifampicin resistance risks relative to dual-drug regimens.
Treatment groups
350 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Group A without complicationsActive comparator 1 intervention
Group B: Group B without complicationsExperimental treatment 1 intervention
Group C: Group C without complicationsExperimental treatment 1 intervention
Group D: Group A of Brucellosis complicated by osteoarticular complicationsActive comparator 1 intervention
Group E: Group B of Brucellosis complicated by osteoarticular complicationsExperimental treatment 1 intervention
Group F: Group C of Brucellosis complicated by osteoarticular complicationsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
clinical cure rate in 6 weeks(body temperature returns to normal, symptoms are relieved)
The proportion of participants achieving clinical cure at 6-week treatment completion, defined as body temperature returning to normal and relief of clinical symptoms.
Time frame
End of treatment (Week 6)2
six - month recurrence rate
The proportion of participants with disease recurrence within 6 months after treatment initiation.
Time frame
6 months after treatment initiation3
The time required for the VAS score of joint pain to decrease by ≥50%
The number of days from treatment initiation until the VAS score of joint pain decreases by at least 50%.
Time frame
Baseline (Week0) \During the treatment period (the 3rd month),\end of treatment (Month 6)4
Treatment completion rate (compliance rate > 90%)
The proportion of participants who complete the full treatment course with drug compliance greater than 90%.
Time frame
end of treatment (Month 6)Secondary outcomes
1
incidence rate of adverse events
The proportion of participants experiencing any adverse event during the observation period.
Time frame
Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation2
incidence rate of serious adverse events (SAE)
The proportion of participants experiencing any serious adverse event (SAE) during the observation period.
Time frame
Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation3
abnormal liver function (ALT/AST >3 times the normal value)
The proportion of participants with ALT or AST exceeding 3 times the upper limit of normal.
Time frame
Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation4
Time for body temperature to return to normal
The number of days required for body temperature to return to normal after starting treatment.
Time frame
During treatment (Week 0 to Week 6)Locations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
The First Affiliated Hospital of Shihezi University
Lead sponsor
The Second People's Hospital of Yining, Xinjiang Uyghur Autonomous Region
Collaborator
Qitai Hospital of the Sixth Division, Xinjiang Production and Construction Corps
Collaborator
Yanqi Hospital of the Second Division, Xinjiang Production and Construction Corps
Collaborator
Sixth Division Hospital, Xinjiang Production and Construction Corps (Wujiaqu People's Hospital)
Collaborator
Xinhua Hospital of Ili Kazakh Autonomous Prefecture, Xinjiang
Collaborator
Source ClinicalTrials.gov
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